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Biomedical subjects

M L Lesser

Publications and source records attributed to M L Lesser.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immunochemotherapy for a systemic intracellular infection: accelerated response using interferon-gamma in visceral leishmaniasis.

To determine if cytokine immunotherapy accelerates the response to conventional treatment in visceral leishmaniasis (kala-azar), previously untreated Indian patients were given antimony for 30 days (n = 15) or antimony plus interferon-gamma (IFN-gamma; n = 16). After 10 days, 10 (63%) of 16 patients treated with antimony plus IFN-gamma versus 1 (7%) of 15 randomized to antimony alone were considered cured of parasites (P < .005). On day 20, 14 (93%) of 15 versus 6 (40%) of 15 patients, respectively, were apparent clinical cures (P < .006), and treatment was discontinued early in the 14 IFN-gamma treated responders. Day 30 apparent cure rates (100% vs. 73%) and 6-month ultimate cure responses (87% vs. 60%) were higher in IFN-gamma-treated patients but not statistically different from controls (P > .05). All 13 IFN-gamma-treated subjects who were cured (12 of whom received therapy for 20 days) have remained healthy with follow-up of 14-24 months (mean, 18.9). These results indicate that IFN-gamma successfully accelerates the parasitologic and clinical response to antimony treatment, an effect that should permit shortening the duration of conventional therapy in previously untreated kala-azar.

Adolescent↗
PubMed1995

p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis.

PURPOSE: The present study explores p53 in relation to the following four aspects of node-negative breast carcinoma: epidemiologic risk factors, tumor histopathology, prognosis, and HER2/neu (HER) expression. MATERIALS AND METHODS: Immunohistochemical (IH) staining for p53 was performed on formaldehyde-fixed, paraffin-embedded primary invasive carcinomas from 440 node-negative patients with a median follow-up duration of 119 months. RESULTS: The IH expression, or lack thereof, of p53 separately or in combination with HER did not prove to be prognostically significant and there was no consistent association of p53 with epidemiologic risk factors. p53 was expressed in 68% of medullary carcinomas (MEDs), which is a significantly higher frequency (P < .001) than in lobular (9%) and duct (23%) carcinomas. p53 was not found in some types of low-grade carcinomas (tubular and papillary), and was observed in a minority of mucinous carcinomas. p53 was present significantly more often in carcinomas with high-grade or poorly differentiated nuclear grade than in low- or intermediate-grade tumors. There was an inverse statistically significant relationship between estrogen receptor (ER) positivity and p53 expression. Tumors with the p53(+)/HER(-) immunophenotype tended to be MEDs or duct carcinomas with a marked lymphoplasmacytic reaction. Infiltrating lobular carcinomas (IFLCs) were largely p53(-)/HER(-). p53(+)/HER(+) carcinomas had the best prognosis. The poorest outcome was associated with the p53(-)/HER(+) immunophenotype. This trend was statistically significant for recurrence-free and overall survival in patients with T1NOMO infiltrating duct carcinoma (IFDC). CONCLUSION: The IH demonstration of p53 was not a reliable prognostic indicator in the node-negative breast carcinoma patients studied and it was not associated with major epidemiologic risk factors. The combined immunophenotypic expression of p53 and HER was significantly associated with some histologic types of breast carcinoma and with prognosis in T1NOMO breast carcinoma.

Breast Neoplasms↗
PubMed1994

Improved body weight status as a result of nutrition intervention in adult, HIV-positive outpatients.

OBJECTIVE: Malnutrition is an important consequence of infection with the human immunodeficiency virus (HIV); involuntary weight loss greater than 10% is one criterion that the Centers for Disease Control and Prevention uses for the diagnosis of acquired immunodeficiency syndrome (AIDS). This study was designed to determine whether nutrition intervention in a group of adult, HIV-positive outpatients affected weight maintenance. METHODS: We undertook a retrospective review of 175 patient charts from the AIDS Reproductive Health Clinic and the Center for Special Studies at The New York Hospital. Forty-nine charts were excluded because the patient expressed a desire to reduce weight, discontinued medical care, or died. Seven charts were eliminated because of missing data. In the remaining patients (n = 119), weights were recorded for the initial clinic contact and for a follow-up visit at least 6 months later. Nutrition intervention completed by a registered dietitian was indicated on 42 patient charts (intervention group); intervention included dietary assessment, intake analysis, appropriate counselling, follow-up, and provision of supplements as needed. The remaining 77 charts did not indicate nutrition intervention; this group was called the nonintervention group. Differences between the intervention and nonintervention groups were analyzed using the two-tailed Fisher exact test and the Mann-Whitney nonparametric test. RESULTS: Forty-two subjects (35% of the total) recieved nutrition intervention, including all of those with gastrointestinal problems (n = 10) and wasting (n = 11). Individuals in the intervention group gained a significant (P < .02) 1.2 +/- 11.4 lb (mean +/- standard deviation; median = +3 lb) compared with those in the nonintervention group who lost a mean of 3.5 +/- 12.8 lb (median = -4 lb). Twenty-six subjects (63%) in the intervention group maintained or gained weight compared with 32 subjects (42%), in the nonintervention group. CONCLUSION: The results of this study suggest that nutrition intervention in HIV-infected persons can improve nutritional status and may lead to an enhanced ability to fight infection.

Adult↗
PubMed1994

Immunohistochemical detection of cathepsin D in T2N0M0 breast carcinoma.

Recent studies have reported significant but inconsistent correlations between tumor cathepsin D (CD) concentration and prognosis in breast carcinoma. To investigate the tissue distribution and a prognostic utility of CD in breast carcinoma, 159 cases of T2N0M0 breast carcinoma with a minimum of 10 years' follow-up were studied for CD expression by immunohistochemistry. This group of patients was chosen for study because of current interest in prognostic markers for stage I breast carcinoma and the likelihood that there would be sufficient recurrences in this group to detect significant differences. Seventy-two carcinomas (45%) showed prominent staining of cells composing the tumor. Neoplastic cell staining for CD correlated with well-differentiated architecture, and lack of neoplastic cell CD expression correlated with high nuclear grade and the medullary carcinoma category. Stromal cell (primarily histiocyte) staining in carcinomas was the major contributor to CD expression in 67 of the 159 cases (42%). Intense intratumoral stromal cell staining correlated with absence of estrogen receptors and the medullary carcinoma subtype. There was no significant correlation between disease-free or overall survival and (a) intensity of overall staining for CD, (b) staining of carcinoma cells alone, or (c) staining of nonneoplastic cells within the region of the carcinoma. These results show that a significant proportion of CD activity detected within a tumor by immunohistochemistry may be contributed by nonneoplastic cells, and there is no significant correlation between survival and immunohistochemical detection of CD in T2N0M0 breast cancer.

Analysis of Variance↗
PubMed1994

Pulmonary function abnormalities in thalassemia major and the role of iron overload.

To determine the predominant abnormality of pulmonary function in patients with thalassemia major (TM), we evaluated 29 patients with TM who were receiving hypertransfusion therapy and chelation with desferrioxamine (DFO), and who ranged in age from 6 to 40 yr (mean 19.8 +/- 8.5 yr). A reduction in the total lung capacity (TLC) was the most striking abnormality, found in 21 of 29 patients (79%). Fourteen of these patients (67%) had a moderate or severe reduction in TLC. Expiratory flow rates, FEV1, and FEF25-75 were decreased below predicted values in 48 and 17% of the patients, respectively, but no patients had pure obstructive disease. Significant hypoxemia (oxygen saturation of less than 95%) was observed in only one patient. There was a significant inverse correlation between TLC and patient age (p < 0.003), transfusional iron burden (p < 0.003) and DFO ratio (p < 0.024). Restrictive disease is the predominant abnormality of pulmonary function in TM, with a mixed restrictive-obstructive pattern in a small number of patients. The restrictive disease becomes more severe with increasing age, and the degree and duration of iron overload appear to be important in its pathogenesis. The role of DFO therapy in preventing the pulmonary complications associated with TM requires further study.

Adolescent↗
PubMed1994

Luteinizing hormone pulsatility in subjects with 5-alpha-reductase deficiency and decreased dihydrotestosterone production.

The pattern of LH pulsatility in male pseudohermaphrodites with inherited 5 alpha-reductase-2 deficiency (5 alpha RD) and decreased levels of plasma dihydrotestosterone was compared to that in normal males. Analysis of 10-min plasma LH sampling during either a 10- or 24-h period demonstrated that the subjects with 5 alpha RD had 1) a mean plasma LH level, mean LH pulse amplitude, and mean plasma LH nadir that were approximately twice normal; and 2) a mean LH pulse frequency similar to that in normal males, whether described as pulses per h or pulses per study period. An increased plasma LH response to GnRH administration was also noted. The findings suggest that a deficiency of DHT results in decreased negative feedback at the level of the hypothalamus and/or pituitary, resulting in an increase in mean plasma LH, LH pulse amplitude, and LH responsiveness to GnRH. In response to increased LH, mean plasma testosterone (T), free T, and plasma estradiol (E2) are increased. The pulse amplitude is increased despite elevated plasma T and E2 levels; this underscores the importance of DHT in pulse amplitude regulation. LH pulse frequency is not decreased despite elevated plasma T and E2, raising the possibility that DHT deficiency increased pulse frequency that was normalized by increased T and/or E2. In conclusion, studies of LH pulsatility in subjects with 5 alpha RD suggest a role for DHT in the modulation of LH.

Adult↗
PubMed1994

Dysphagia therapy following stroke: a controlled trial.

OBJECTIVE: To determine the effect of graded levels of intervention by a dysphagia therapist on the occurrence of pneumonia, dehydration, calorie-nitrogen deficit, recurrent upper airway obstruction, and death following stroke. DESIGN: A randomized control trial. SETTING: Inpatient stroke rehabilitation unit. PATIENTS: All patients met the following eligibility criteria: (1) stroke defined by clinical history and neurologic examination with compatible CT or MRI, (2) ages 20 to 90 years inclusive, (3) no known history of significant oral or pharyngeal anomaly, (4) laboratory values below end point criteria, (5) failure on the Burke Dysphagia Screening Test, and (6) modified barium swallow evaluation evidence of dysphagia (patients who aspirated > or = 50% of all consistencies presented, even using compensatory swallowing techniques, were excluded). Of 123 eligible patients, eight refused study participation. One hundred fifteen patients were randomized. INTERVENTIONS: Three graded levels of dysphagia therapist control of diet consistency and reinforcement of compensatory swallowing techniques were provided during the inpatient rehabilitation stay. MAIN OUTCOME MEASURES: Pneumonia, dehydration, calorie-nitrogen deficit, recurrent upper airway obstruction, and death. RESULTS: The log rank statistic showed no significant difference between the three treatment groups for the distribution of time until end point during the inpatient stay or to 1 year post-stroke. CONCLUSION: Limited patient and family instruction regarding use of diet modification and compensatory swallowing techniques during inpatient rehabilitation is as effective as therapist control of diet consistency and daily rehearsal of compensatory swallowing techniques for the prevention of medical complications associated with dysphagia following stroke.

Aged↗
PubMed1994

Late effects of bone marrow transplantation on pulmonary function in children.

This study was undertaken to evaluate in a primarily pediatric population whether the late effects of bone marrow transplantation (BMT) on pulmonary function in patients having undergone the procedure for treatment of acute leukemia or lymphoma are worse than that of patients having undergone transplant for treatment of aplastic anemia. Forty-six patients were studied. We did not demonstrate statistically significant differences in group mean forced expiratory flow in one second/forced vital capacity (FEV1/FVC) and percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% of the forced vital capacity (FEF25-75) and total lung capacity (TLC) values between the two groups of patients before BMT and to 7 years post-transplant. Individual patients with pulmonary function abnormalities were identified. Furthermore, there were no significant differences between the two study groups or within the group of patients with aplastic anemia from pre-transplant to 9-12 months and from pre-transplant to 18-24 months after BMT. However, within the group of patients treated for acute leukemia or lymphoma, there was a significant decline in the group mean percentage predicted FVC (p = 0.0001), FEV1 (p = 0.0006) and FEF25-75 (p = 0.0063) from pre-transplant to 9-12 months and in the FVC (p = 0.004) and FEV1 (p = 0.0006) from pre-transplant to 18-24 months after BMT. The greater decline in the FVC relative to the FEV1 suggests the development of a restrictive process in this group of patients.

Adolescent↗
PubMed1992

Obesity at diagnosis of breast carcinoma influences duration of disease-free survival.

OBJECTIVE: To study disease-free survival at 10 years in relation to obesity at the time of diagnosis. DESIGN: A prospective study of consecutively treated patients with primary breast cancer. SETTING: Memorial Sloan-Kettering Cancer Center, New York. PATIENTS: Nine hundred twenty-three women treated by mastectomy and axillary dissection. MAIN RESULTS: Women who were obese (25% or more over optimal weight for height) at the time of primary breast cancer treatment were at significantly greater risk for recurrence (42%) compared with nonobese patients (32%) 10 years after diagnosis (P less than 0.01). In multivariate analyses, obesity remained a statistically significant prognostic factor after controlling for measured tumor size, number of positive axillary lymph nodes, age at diagnosis, and adjuvant chemotherapy with a hazard ratio of 1.29 (95% CI, 1.0 to 1.67). When analyses were restricted to the 557 patients free of lymph node metastases, the hazard ratio of recurrence associated with obesity was 1.59 (CI, 1.06 to 2.39); 32% of obese patients developed recurrent disease compared with 19% of nonobese women. CONCLUSIONS: Obesity at the time of diagnosis is a significant prognostic factor that may limit the reduction in breast cancer mortality attainable through detection at an early stage of disease. Because obesity and the risk for breast cancer increase with age, interventions that encourage weight control may influence breast cancer survival rates.

Adult↗
PubMed1992

Chronic graft-versus-host disease and pulmonary function.

Pulmonary complications are a major cause of morbidity and mortality in bone marrow transplant recipients. Earlier series, consisting mainly of adults, have shown evidence of obstructive changes of pulmonary functions in association with chronic graft-versus-host disease (CGVHD). We longitudinally evaluated spirometry in 46 patients who received bone marrow transplants as children or as young adults to determine whether they had similar abnormalities. Group mean FEV1/FVC, and percent predicted FVC, FEV1, and FEF25-75 values did not demonstrate obstructive changes in association with CGVHD in this patient population. Our findings suggest that younger patients with CGVHD, as a group, may fare better than older bone marrow transplant recipients with CGVHD. However, due to small sample sizes, it cannot be conclusively stated that the pulmonary function parameters analyzed do not differ in the two patient groups.

Adolescent↗
PubMed1992

Long-term results of iodine 125 irradiation of uveal melanoma.

The authors report on 64 of the first 65 patients treated with iodine 125. The mean follow-up was 64.9 months. After treatment, 29 patients (45.3%) retained visual acuity of 20/100 or better, and 18 patients (28.1%) retained visual acuity within two lines of visual acuity before irradiation. Eleven patients (17.2%) died of metastasis, and 5 patients (7.8%) had local recurrence. Cataract developed in 29 (45.3%) patients; keratitis developed in only 2 (3.1%) patients, and dry eye developed in none. Neovascular glaucoma developed in 7 (10.9%) patients, and 15 (23.4%) patients had radiation retinopathy. Eleven patients (17.2%) required enucleation for either tumor growth or neovascular glaucoma. These results show the increasing number of radiation complications seen with long-term observation and the frequently seen adverse visual outcome.

Brachytherapy↗
PubMed1991

Timing of breast cancer excision during the menstrual cycle influences duration of disease-free survival.

OBJECTIVE: To study disease-free survival at 10 years in relation to timing of breast tumor excision during the menstrual cycle. DESIGN: A prospective study of consecutively treated patients with primary breast cancer. SETTING: Memorial Sloan-Kettering Cancer Center, New York. PATIENTS: Two hundred and eighty-three premenopausal patients treated by mastectomy and axillary dissection. MAIN RESULTS: When the tumor was excised during the follicular phase, approximated by setting the putative day of ovulation on day 14 after the onset of last menses, a higher recurrence risk (43%) was observed compared with excision later in the menstrual cycle (29%, P = 0.02). The rate peaked among patients treated between days 7 and 14 and was lowest between days 20 and 30. Multivariate analysis using the Cox regression model to control for tumor size, nodal status, estrogen receptor status, adjuvant chemotherapy, and family history indicated that the hazard rate of breast cancer recurrence after excision during the follicular phase was 1.53 (95% Cl, 1.02 to 2.29). Stratification by nodal status indicated that the effect of phase was statistically significant only among patients with positive nodes (hazard ratio, 2.10; Cl, 1.19 to 3.70). CONCLUSIONS: Our results support the hypothesis that the risk for recurrence may be affected by the hormonal milieu of the menstrual cycle; these findings must be confirmed, however, by a prospective study in which cycle phase at time of tumor excision is biochemically documented.

Adult↗
PubMed1991

Prolonged survival in patients with beta-thalassemia major treated with deferoxamine.

To determine whether survival of patients with beta-thalassemia major has been prolonged by management that utilizes hypertransfusion and chelation with deferoxamine, we analyzed longevity by the Kaplan-Meier product-limit method. Group 1 patients (n = 71) followed between 1960 and 1976 with a low-transfusion regimen (pretransfusion hemoglobin level 7 to 8 gm/dl) and no chelation had an estimated median age of survival of 17.4 years, whereas it was 31.0 years for group 2 subjects (n = 80), who began hypertransfusion between 1976 and 1978 (pretransfusion hemoglobin level 10.5 to 11.5 gm/dl) and chelation with deferoxamine (20 to 60 mg/kg per day) (p less than 0.0001). For 70 patients who were treated with hypertransfusion and deferoxamine, we had data to calculate the ratio of total milligrams of transfusional iron to cumulative grams of deferoxamine. The 24 patients who died had a total iron burden of greater than 1.05 gm/kg; the ratio for them exceeded 31. These patients were characterized by poor compliance with chelation or by late start of therapy, with inability to receive enough deferoxamine before death. Death was preceded by arrhythmia requiring therapy in all but one, and by cardiac failure in all. Of 41 similarly iron-loaded survivors, 33 had a ratio of less than 31; only three had an arrhythmia, and five had cardiac failure. We conclude that treatment with deferoxamine, when used in amounts proportional to iron burden, delayed cardiac complications and improved longevity.

Adolescent↗
PubMed1991

Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases.

We used monoclonal antibodies to identify occult micrometastases in the bone marrow of 49 patients with operable (stage I and II) breast carcinoma. Follow-up (mean, 29 months; median, 30 months) revealed that 12 patients recurred. The presence of bone marrow micrometastases (BMM) was significantly associated with early recurrence (P less than .04). The estimated 2-year recurrence rate for patients with no BMM detected (BMM-) was 3%; in patients with BMM, the 2-year recurrence rate was 33%. When BMM and axillary lymph node (LN) status were combined, groups of patients at low risk (LN-, BMM-; 2-year recurrence rate, 0%) and high risk (LN+, BMM+; 2-year recurrence rate, 42%) for early recurrence were identified. Bone marrow tumor burden was related to early recurrence. Among patients with BMM, those who did not recur had on average fewer extrinsic cells in their marrow than those who recurred (15 v 43 cells, respectively). Multivariate analysis comparing BMM, LN+ versus LN-, and tumor size (less than or equal to 2 cm v greater than 2 cm) revealed no factor independently associated with early recurrence. Peripheral tumor burden of BMM (0 or less than 10 extrinsic cells v greater than or equal to 10 extrinsic cells) was the only independent predictor of early recurrence (P less than .003). In conjunction with conventional prognostic factors, particularly axillary LN status, evaluation for BMM might be used to stratify patients for adjuvant treatment programs. Because this pilot study involved few patients with short-term follow-up, the results should be interpreted with caution. The examination of bone marrow for micrometastases remains an experimental procedure; the clinical usefulness of the test will be established through larger studies with long-term follow-up.

Antibodies, Monoclonal↗
PubMed1990

The two patterns of reactive astrocytosis in postischemic rat brain.

The distribution and time course of postischemic astrocyte hypertrophy and hyperplasia and the relationship to neuronal viability or necrosis was studied in rats subjected to 30 min of carotid and vertebral artery occlusion followed by reperfusion from 3 h to 5 weeks. Intermediate filaments (IFs) were evaluated by electron microscopy, IF proteins by immunohistochemistry, and astrocyte division by [3H]thymidine uptake. Glial fibrillary acidic protein (GFAP) increased in damaged and nondamaged brain regions by 2 days and was associated with cell enlargement, increases in IF, and transformation of GFAP-negative into GFAP-positive glia. Cell hypertrophy and increased GFAP persisted only in regions of neuronal necrosis whereas the number and size of GFAP-positive astrocytes returned to control levels in nondamaged regions by 2 weeks. Astrocyte hyperplasia was not seen until 3 days and was confined to damaged brain regions. Vimentin-positive astrocytes were numerous by 2 days in damaged brain and remained only in those regions at 5 weeks. The data demonstrate that reactive astrocytosis develops in undamaged brain, but is reversible with prolonged survival, whereas reactive astrocytosis that accompanies structural brain damage persists for prolonged periods and is associated with hyperplasia, as well as hypertrophy. In addition, the results show that astrocyte expression of vimentin is more specific than GFAP in identifying regions of permanent ischemic injury during the early postischemic period.

Animals↗
PubMed1989

DNA content of rectal scrapings from individuals at low and high risk for the development of colorectal cancer. A feasibility study.

Scrapings of superficial rectal mucosa were collected from 31 patients with colorectal carcinoma, 66 patients with sporadic adenoma, and 53 control subjects with no personal or family history of colorectal cancer. The DNA ploidy level and proliferative patterns of each specimen were analyzed by flow cytometry (FCM). A GMS index, calculated as the ratio of G2 + M:S, was found to be significantly lower in control subjects than in any of the high-risk groups studied. Aneuploidy was more prevalent in rectal scrapings from cancer patients and adenoma patients than in those from control subjects. Aneuploid cell populations were detected in apparently normal rectal scrapings from two control subjects. Some high-risk individuals (i.e., cancer patients and patients with adenomas and a family history of cancer) exhibited higher proportions of tetraploid (designated G2/M) cells and a higher G2/M:S phase ratio than control subjects. The results accumulated thus far show that the rectal scraping procedure is safe and easy to perform. Our limited findings give hope that the DNA content analysis of cells obtained by rectal scraping may eventually prove useful in mass screening for colorectal cancer risk. However, definitive evaluation will require further refinement and elaboration of analytic technique and testing on more patients at various levels of predetermined risk.

Adenoma↗
PubMed1989

Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis.

Over a 4-year period in a chemoprevention trial on large bowel neoplasia, 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid (vitamin C)/day plus 400 mg of alpha-tocopherol (vitamin E)/day alone or with a grain fiber supplement (22.5 g/day). In this randomized, double-blind, placebo-controlled study, we determined the effects of these supplements on rectal polyps in these patients. Analysis by intent to treat suggested that the high-fiber supplement had a limited effect. Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial. The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population. The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia.

Adenomatous Polyposis Coli↗